Endothelin receptor antagonists

ABSTRACT

This invention relates to pyridizinone derivatives of formula I ##STR1## wherein the various substituents are defined in the specification, and salts thereof, which have useful pharmacological properties, in particular endothelin receptor-antagonistic properties. The compounds are thus useful for the treatment of illnesses associated with endothelin activities, such as hypertension, cardiac insufficiency, coronary heart disease, renal, cerebral and myocardial ischaemia, renal insufficiency, cerebral infarct, subarachnoid haemorrhage, arteriosclerosis pulmonary high blood pressure, inflammations, asthma, prostate hyperplasia, endotoxic shock and in complications after the administration of immunosuppressants which produce renal vasoconstriction.

This is a 371 application of PCT/EP96/04111, filed on Sep. 19, 1996.

The invention relates to compounds of the formula I ##STR2## in which Yis --C(R⁴ R^(4'))C(R⁴ R^(4')), --CR⁴ ═CR^(4') -- or C(R⁴ R⁴)S--,

R¹ is Het, Ar, R³ or R⁴,

R² is Ar or a ##STR3## which is unsubstituted or mono- or disubstitutedin the phenyl moiety by A, R³, OR⁴, NH₂, NHA, NA₂, NO₂, CN, Hal, NHCOR⁴,NHSO₂ R⁴, COOR⁴, COR⁴, CONHSO₂ R⁶, O(CH₂)_(n) R³, OPh, O(CH₂)_(n) OR⁴ orS(O)_(m) R⁴ or

a ##STR4## which is unsubstituted or mono- or disubstituted in thecyclohexyldienyl moiety by A, R³, OR⁴, NH₂ , NHA, NA₂, NO₂, CN, Hal,NHCOR⁴, NHSO₂ R⁴, COOR⁴, COR⁴, CONHSO₂ R⁶, O(CH₂)_(n) R³, OPh,O(CH₂)_(n) OR⁴ or S(O)_(m) R⁴,

R³ is CN, COOH, COOA, CONHSO₂ R⁵ or 1H-tetrazol-5-yl,

R⁴,R^(4') in each case independently of one another are H, A or

phenyl or benzyl which is unsubstituted or monosubstituted by alkoxy,

R⁵ is A or Ar,

R⁶ is phenyl or naphthyl which is unsubstituted or mono-, di- ortrisubstituted by A, OR⁵, NH₂, NHA, NA₂, NO₂, CN or Hal,

A is alkyl having 1-6 C atoms, in which one or two CH₂ groups can bereplaced by O or S atoms or by --CR⁴ ═CR⁴, groups and also 1-7 H atomscan be replaced by F, or is benzyl,

Ar is phenyl or naphthyl, which is unsubstituted or mono-, di- ortrisubstituted by A, OR⁴, NH₂, NHA, NA₂, NO₂, CN, Hal, NHCOR⁴, NHSO₂ R⁴,COOR⁴, COR⁴, CONHSO₂ R⁶, O(CH₂)_(n) R³, OPh, O(CH₂)_(n) OR⁴ or S(O)_(m)R⁴,

Het is a mono- or binuclear saturated, unsaturated or aromaticheterocycle having 1 to 4 N, O and/or S atoms, bonded via N or C, whichcan be unsubstituted or mono-, di- or trisubstituted by Hal, A, R³, NH₂,NHA, NA₂, CN, NO₂ and/or carbonyl oxygen,

D is carbonyl or C(R⁴ R^(4'))!_(n),

E is CH₂, S or O,

Hal is F, Cl, Br or I,

X is O or S,

m is 0, 1 or 2,

n is 1 or 2,

and their salts.

Similar compounds having indan and indene parent structures aredisclosed in WO 93/08799, those with indole systems are disclosed in WO94/14434, pyrimidine derivatives are disclosed in EP 0 526 708 A1 andphenyl and naphthyl compounds are disclosed in EP 0 617 001 A.

The invention was based on the object of finding novel compounds havinguseful properties, in particular those which can be used for theproduction of medicaments.

It has been found that the compounds of the formula I and their saltshave very useful pharmacological properties combined with goodtolerability. In particular, they exhibit endothelinreceptorantagonistic properties and can therefore be employed for thetreatment of illnesses such as hypertension, cardiac insufficiency,coronary heart disease, renal, cerebral and myocardial ischaemia, renalinsufficiency, cerebral infarct, subarachnoid haemorrhage,arteriosclerosis, pulmonary high blood pressure, inflammations, asthma,prostate hyperplasia, endotoxic shock and in complications after theadministration of immunosuppressants, such as, for example, cyclosporin,which can produce renal vasoconstriction, as well as other illnessesassociated with endothelin activities.

The compounds exhibit, inter alia, a high affinity for the endothelinsubreceptors ET_(A) and ET_(B). These actions can be determined bycustomary in vitro or in vivo methods, such as, for example, describedby P. D. Stein et al., J. Med. Chem. 37, 1994, 329-331 and E. Ohlsteinet al., Proc. Natl. Acad. Sci. USA 91, 1994, 8052-8056.

A suitable method for the determination of the hypertensive action is,for example, described by M. K. Brazil et al., J. Cardiovasc. Pharmacol.22, 1993, 897-905 and J. Lange et al., Lab Animal 20, 1991, Appl. Note1016.

The compounds of the formula I can be employed as pharmaceutical activecompounds in human and in veterinary medicine, in particular for theprophylaxis and/or therapy of cardiac, circulatory and vasculardiseases, especially of hypertension and cardiac insufficiency.

The invention relates to the compounds of the formula I and their salts,and to a process for the preparation of these compounds and their salts,characterized in that

a compound of the formula II ##STR5## in which R¹ and Y have the meaningindicated in Claim 1,

is reacted with a compound of the formula III ##STR6## in which Q is Cl,Br, I or a free or reactive functionally modified OH group and

R² and R³ have the meaning indicated in Claim 1,

and/or in that in a compound of the formula I one or more radicals R¹,R² and/or R³ are converted into one or more radicals R¹, R² and/or R³,by, for example,

i) hydrolysing an ester group to a carboxyl group,

ii) converting a carboxyl group into a sulfonamidocarbonyl group

and/or converting a base or acid of the formula I into one of its salts.

In the above formulae, A has 1 to 6, preferably 1, 2, 3 or 4 carbonatoms. A is preferably methyl, furthermore ethyl, propyl, isopropyl,butyl, isobutyl, sec-butyl or tert-butyl, furthermore also pentyl, 1-,2- or 3-methylbutyl, 1,1-, 1,2- or 2,2-dimethylpropyl, 1-ethylpropyl,hexyl, 1-, 2-, 3- or 4-methylpentyl, 1,1-, 1,2-, 1,3-, 2,2-, 2,3- or3,3-dimethylbutyl, 1- or 2-ethylbutyl, 1-ethyl-1-methylpropyl,1-ethyl-2-methylpropyl, 1,1,2- or 1,2,2-trimethylpropyl, furthermoretrifluoromethyl or pentafluoroethyl. Furthermore, A is cycloalkyl,preferably cyclopropyl.

E is preferably O, furthermore also CH₂ or S.

D is preferably CH₂, likewise carbonyl is also preferred.

n is preferably 1, furthermore preferably 2.

Hal is preferably F, Cl or Br, but also I.

Alkoxy is preferably methoxy, furthermore ethoxy, propyloxy, butyloxy orpentyloxy.

Ar is unsubstituted, preferably--as indicated--monosubstituted phenyl,specifically preferably phenyl, o-, m- or p-tolyl, o-, m- orp-ethylphenyl, o-, m- or p-propylphenyl, o-, m- or p-isopropylphenyl,o-, m- or p-tert-butylphenyl, o- m- or p-trifluoromethylphenyl, o-, m-or p-hydroxyphenyl, o-, m- or p-nitrophenyl, o-, m- or p-aminophenyl,o-, m- or p-(N-methylamino)-phenyl, o-, m- or p-acetamidophenyl, o-, m-or p-(trifluoromethoxy)phenyl, o-, m- or p-cyanophenyl, o-, m- orp-methoxyphenyl, o-, m- or p-ethoxyphenyl, o-, m- or p-carboxyphenyl,o-, m- or p-methoxy-carbonylphenyl, o-, m- or p-ethoxycarbonylphenyl,o-, m- or p-benzyloxycarbonylphenyl, o-, m- or p-(carboxymethoxy)phenyl,o-, m- or p-(methoxy-carbonyl-methyoxy) phenyl, o-, m- orp-(methoxycarbonyl-ethoxy) phenyl, o-, m- orp-(N,N-dimethylamino)phenyl, o-, m- or p-(N-ethylamino)phenyl, o-, m- orp-(N,N-diethylamino)phenyl, o-, m- or p-fluorophenyl, o-, m- orp-bromophenyl, o-, m- or p-chlorophenyl, o-, m- orp-(difluoromethoxy)phenyl, o-, m- or p-(fluoromethoxy)phenyl, o-, m- orp-formylphenyl, o-, m- or p-acetylphenyl, o-, m- or p-propionylphenyl,o-, m- or p-butyrylphenyl, o-, m- or p-pentanoylphenyl, o-, m- orp-(phenylsulfonamidocarbonyl)phenyl, o-, m- or p-phenoxyphenyl, o-, m-or p-methylthiophenyl, o-, m- or p-methylsulfinylphenyl, o-, m- orp-methylsulfinylphenyl, o-, m- or p-benzyloxyphenyl, o-, m- orp-cyanomethoxyphenyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or 3,5-(difluoromethoxy) (carboxymethoxy)phenyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4-or 3,5-methoxy-(carboxymethoxy)phenyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or3,5-hydroxy(carboxymethoxy)phenyl, furthermore preferably 2,3-, 2,4-,2,5-, 2,6-, 3,4- or 3,5-difluorophenyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or3,5-dichlorophenyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or 3,5-dibromophenyl,2-chloro-3-methyl-, 2-chloro-4-methyl-, 2-chloro-5-methyl-,2-chloro-6-methyl-,2-methyl-3-chloro-, 2-methyl-4-chloro-,2-methyl-5-chloro-, 2-methyl-6-chloro, 3-chloro-4-methyl,3-chloro-5-methyl- or 3-methyl-4-chlorophenyl, 2-bromo-3-methyl,2-bromo-4-methyl, 2-bromo-5-methyl-, 2-bromo-6-methyl,2-methyl-3-bromo-, 2-methyl-4-bromo-, 2-methyl-5-bromo-,2-methyl-6-bromo-, 3-bromo-4-methyl, 3-bromo-5-methyl- or3-methyl-4-bromophenyl, 2,4- or 2,5-dinitrophenyl, 2,5- or3,4-dimethoxyphenyl, 3-nitro-4-chlorophenyl, 2-amino-3-chloro-,2-amino-4-chloro, 2-amino-5-chloro- or 2-amino-6-chlorophenyl,2-nitro-4-N,N-dimethylamino or 3-nitro-4-N,N-dimethyl-aminophenyl,2,3,4-, 2,3,5-, 2,3,6-, 2,4,6- or 3,4,5-trichlorophenyl,2,4,6-tri-tert-butylphenyl, furthermore preferably2-nitro-4-(trifluoromethyl)phenyl, 3,5-di-(trifluoromethyl)phenyl,2,5-dimethylphenyl, 2-hydroxy-3,5-dichlorophenyl, 2-fluoro-5- or4-fluoro-3-(trifluoromethyl)phenyl, 4-chloro-2- or4-chloro-3-(trifluoromethyl), 2-chloro-4- or2-chloro-5-(trifluoromethyl)phenyl, 4-bromo-2- or4-bromo-3-(trifluoromethyl)phenyl, p-iodophenyl,2-nitro-4-methoxyphenyl, 2,5-dimethoxy-4-nitrophenyl,2-methyl-5-nitrophenyl, 2,4-dimethyl-3-nitrophenyl,3,6-dichloro-4-aminophenyl, 4-fluoro-3-chlorophenyl,4-fluoro-3,5-dimethylphenyl, 2-fluoro-4-bromophenyl,2,5-difluoro-4-bromophenyl, 2,4-dichloro-5-methylphenyl,3-bromo-6-methoxyphenyl, 3-chloro-6-methoxyphenyl,2-methoxy-5-methylphenyl, 2,4,6-triisopropylphenyl, naphthyl or5-dimethylamino-1-naphthyl (dansyl).

Het is preferably 2- or 3-furyl, 2- or 3-thienyl, 1-,2- or 3-pyrrolyl,1-, 2,4- or 5-imidazolyl, 1-, 3-, 4- or 5-pyrazolyl, 2-, 4- or5-oxazolyl, 3-, 4- or 5-isoxazolyl, 2-, 4- or 5-thiazolyl, 3-, 4- or5-isothiazolyl, 2-, 3- or 4-pyridyl, 2-, 4-, 5- or 6-pyrimidinyl,furthermore preferably 1,2,3-triazol-1-, -4- or -5-yl, 1,2,4-triazol-1-,-3- or -5-yl, 1- or 5-tetrazolyl, 1,2,3-oxadiazol-4- or -5-yl,1,2,4-oxadiazol-3- or 5-yl, 1,3,4-thiadiazol-2- or -5-yl,1,2,4-thiadiazol-3- or -5-yl, 1,2,3-thiadiazol-4- or -5-yl, 2-, 3-, 4-,5- or 6-2H-thiopyranyl, 2-, 3- or 4-4-H-thiopyranyl, 3- or4-pyridazinyl, pyrazinyl, 2-, 3-, 4-, 5- 6- or 7-benzofuryl, 2-, 3-, 4-,5-, 6- or 7-benzothienyl, 1-, 2-, 3-, 4-, 5-, 6- or 7-indolyl, 1-, 2-,4- or 5-benzimidazolyl, 1-, 3-, 4-, 5-, 6- or 7-benzopyrazolyl, 2-, 4-,5-, 6- or 7-benzoxazolyl, 3-, 4-, 5-, 6- or 7-benzoisoxazolyl, 2-, 4-,5-, 6- or 7-benzothiazolyl, 2-, 4-, 5-, 6- or 7-benzisothiazolyl, 4-,5-, 6- or 7-benzo-2,1,3-oxadiazolyl, 2-, 3-, 4-, 5-, 6-, 7- or8-quinolyl, 1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolyl, 3-, 4-, 5-, 6-, 7-or 8-quinolinyl, 2-, 4-, 5-, 6-, 7- or 8-quinazolinyl. The heterocyclicradicals can also be partially or completely hydrogenated. Het can thus,for example, also be 2,3-dihydro-2-, -3-, -4- or -5-furyl,2,5-dihydro-2-, -3-, -4- or 5-furyl, tetrahydro-2- or -3-furyl,1,3-dioxolan-4-yl, tetrahydro-2- or -3-thienyl, 2,3-dihydro-1-, -2-,-3-, -4- or -5-pyrrolyl, 2,5-dihydro-1-, -2-, -3-, -4- or -5-pyrrolyl,1-, 2- or 3-pyrrolidinyl, tetrahydro-1-, -2- or -4-imidazolyl,2,3-dihydro-1-, -2-, -3-, -4- or -5-pyrazolyl, tetrahydro-1-, -3- or-4-pyrazolyl, 1,4-dihydro-1-, -2-, -3- or -4-pyridyl,1,2,3,4-tetrahydro-1-, -2-, -3-, -4-, -5- or -6-pyridyl, 1-, 2-, 3- or4-piperidinyl, 2-, 3- or 4-morpholinyl, tetrahydro-2-, -3- or-4-pyranyl, 1,4-dioxanyl, 1,3-dioxan-2-, -4- or -5-yl, hexahydro-1-, -3-or -4-pyridazinyl, hexahydro-1-, -2-, -4- or -5-pyrimidinyl, 1-, 2- or3-piperazinyl, 1,2,3,4-tetrahydro-1-, -2-, -3-, -4-, -5-, -6-, -7- or-8-quinolyl, 1,2,3,4-tetrahydro-1-, -2-, -3-, -4-, -5-, -6-, -7- or-8-isoquinolyl.

The radical R² is preferably Ar, 2,3-methylenedioxyphenyl,3,4-methylenedioxyphenyl, 2,3-ethylenedioxyphenyl,3,4-ethylenedioxyphenyl, 2,3-(2-oxomethylenedioxy)phenyl, 2,3-, 2,4-,2,5-, 2,6-, 3,4- or 3,5- (difluoromethoxy) (carboxymethoxy)phenyl, 2,3-,2,4-, 2,5-, 2,6-, 3-4- or 3,5-methoxy-(carboxymethoxy)phenyl, 2,3-,2,4-, 2,5-, 2,6-, 3,4- or 3,5-hydroxy-(carboxymethoxy)phenyl.

R² is furthermore preferably 2,3-dihydrobenzofuranyl,2,3-dihydro-2-oxofuranyl, furthermore preferably2,1,3-benzothiadiazol-4- or -5-yl or 2,1,3-benzoxadiazol -5-yl.

The radical R³ is preferably carbomethoxy, carboethoxy, carbopropoxy,carbobutoxy, carbobenzyloxy, furthermore cyano, 1H-tetrazol-5-yl orcarboxyl, but particularly preferably is phenylsulfonamidocarbonyl or4-alkyl-phenylsulfonamidocarbonyl.

It applies to the entire invention that all radicals which occurrepeatedly, such as, for example, R⁴, R^(4') or R⁵ can be identical ordifferent, i.e. are independent of one another. If, for example, Y is--C(R⁴ R^(4'))C(R⁴ R^(4'))--, the two C atoms can also be identically ordifferently substituted.

Accordingly, the invention relates in particular to those compounds ofthe formula I in which at least one of the radicals mentioned has one ofthe preferred meanings indicated above. Some preferred groups ofcompounds can be expressed by the following subformulae Ia to Ih, whichcorrespond to the formula I and in which the radicals which are notdescribed in greater detail have the meaning indicated in formula I, butin which

in Ia Y is --CH² --CH² ;

in Ib Y is --CH═CH--;

in Ic Y is --CH₂ --S--;

in Id Y is --C(R⁴ R^(4'))C(R⁴ R^(4')) and

R² is a ##STR7## in Ie Y is --CR⁴ ═CR⁴ -- and R² is a ##STR8## in If Yis --C(R⁴ R^(4'))C(R⁴ R^(4')) and R² is Ar;

in Ig Y is --C(R⁴ R^(4'))C(R⁴ R^(4')),

R¹ is Ar and

R³ is CONHSO₂ R⁵ ;

in Ih Y is --C(R⁴ R^(4'))C(R⁴ R^(4')),

R¹ is Ar,

R² is a ##STR9## and R³ is CONHSO₂ R⁵ ;

The compounds of the formula I and also the starting substances fortheir preparation are otherwise prepared by methods known per se, suchas are described in the literature (e.g. in the standard works such asHouben-Weyl, Methoden der organischen Chemie Methods of OrganicChemistry!, Georg-Thieme-Verlag, Stuttgart; but in particular in EP 0617 001 A1), namely under reaction conditions which are known andsuitable for the reactions mentioned. Use can also be made in this caseof variants which are known per se, but not mentioned here in greaterdetail.

The starting substances, if desired, can also be formed in situ so thatthey are not isolated from the reaction mixture, but immediately reactedfurther to give the compounds of the formula I.

Compounds of the formula I can preferably be obtained by reactingcompounds of the formula II with compounds of the formula III.

In the compounds of the formula III, Q is preferably Cl, Br, I or areactive modified OH group such as alkylsulfonyloxy having 1-6 C atoms(preferably methylsulfonyloxy) or arylsulfonyloxy having 6-10 C atoms(preferably phenyl- or p-tolylsulfonyloxy).

The reaction is generally carried out in an inert solvent, in thepresence of an acid-binding agent, preferably of an alkali metal oralkaline earth metal hydroxide, carbonate or bicarbonate or of anothersalt of a weak acid of the alkali metals or alkaline earth metals,preferably of potassium, sodium, calcium or caesium. The addition of anorganic base such as triethylamine, dimethylaniline, pyridine orquinoline or of an excess of the phenol component of the formula II orof the alkylation derivative of the formula III may be favourable. Thereaction time, depending on the conditions used, is between a fewminutes and 14 days and the reaction temperature is betweenapproximately 0° and 150°, normally between 20° and 130°.

Suitable inert solvents are, for example, hydrocarbons such as hexane,petroleum ether, benzene, toluene or xylene; chlorinated hydrocarbonssuch as trichloroethylene, 1,2-dichloroethane, carbon tetrachloride,chloroform or dichloromethane; alcohols such as methanol, ethanol,isopropanol, n-propanol, n-butanol or tert-butanol; ethers such asdiethyl ether, diisopropyl ether, tetrahydrofuran (THF) or dioxane;glycol ethers such as ethylene glycol monomethyl or monoethyl ether(methyl glycol or ethyl glycol), ethylene glycol dimethyl ether(diglyme); ketones such as acetone or butanone; amides such asacetamide, dimethylacetamide or dimethylformamide (DMF); nitriles suchas acetonitrile; sulfoxides such as dimethyl sulfoxide (DMSO); carbondisulfide; carboxylic acids such as formic acid or acetic acid; nitrocompounds such as nitromethane or nitrobenzene; esters such as ethylacetate or mixtures of the solvents mentioned.

The starting compounds of the formulae II and III are known in somecases, but in some cases are alternatively novel. The novel compounds,however, can be prepared by methods known per se. Thus, for example,6-(2,4-dimethoxyphenyl)-2,3-dihydropyridazin-3-one can be obtained byreaction of 4-(2,4-dimethoxyphenyl)-4-oxobutanoic acid with hydrazineand subsequent reaction of the6-(2,4-dimethoxyphenol)-2,3,4,5-tetrahydropyridazin-3-one formed withbromine. Furthermore, for example, methyl benzo1,3!dioxol-5-yl-bromoacetate can be obtained by reaction of methyl benzo1,3!-dioxol-5-ylhydroxyacetate with phosphorus tribromide. This reactionis expediently carried out at temperatures between 0° and approximately200°; preferably between 30° and 80°. Suitable inert solvents are thosealready mentioned above.

It is furthermore possible to convert a compound of the formula I intoanother compound of the formula I by converting one or more radicalsR¹,R² and/or R³ into one or more other radicals R¹,R² and/or R ³, e.g.by hydrolysing an ester group to a carboxyl group and/or converting acarboxyl group into a sulfonamidocarbonyl group.

Furthermore, free amino groups can be acylated in the customary mannerusing a sulfonyl chloride or sulfonic anhydride or alkylated using anunsubstituted or substituted alkyl halide, expediently in an inertsolvent such as dichloromethane or THF and/or in the presence of a basesuch as triethylamine or pyridine at temperatures between -60° and +30°.

If desired, a functionally modified amino and/or hydroxyl group in acompound of the formula I can be liberated by solvolysis orhydrogenolysis according to customary methods. Thus, for example, acompound of the formula I which contains an NHCOR or a COOR group can beconverted into the corresponding compound of the formula I which,instead of this, contains an NH₂ - or an HOOC-group. COOR⁴ groups can behydrolysed, for example, using NaOH or KOH in water, water-THF orwater-dioxane at temperatures between 0° and 100°.

A base of the formula I can be converted into the associated acidaddition salt using an acid, for example by reaction of equivalentamounts of the base and of the acid in an inert solvent such as ethanoland subsequent evaporation. Suitable acids for this reaction areparticularly those which give physiologically acceptable salts. Thusinorganic acids can be used, e.g. sulfuric acid, nitric acid, hydrohalicacids such as hydrochloric acid or hydrobromic acid, phosphoric acidssuch as orthophosphoric acid, sulfamic acid, furthermore organic acids,in particular aliphatic, alicyclic, araliphatic, aromatic or hetercyclicmono- or polybasic carboxylic, sulfonic or sulfuric acids, e.g. formicacid, acetic acid, propionic acid, pivalic acid, diethylacetic acid,malonic acid, succinic acid, pimelic acid, fumaric acid, maleic acid,lactic acid, tartaric acid, malic acid, citric acid, gluconic acid,ascorbic acid, nicotinic acid, isonicotinic acid, methane- orethanesulfonic acid, ethanedisulfonic acid, 2-hydroxyethanesulfonicacid, benzenesulfonic acid, p-toluenesulfonic acid, naphthalenemono- anddisulfonic acids, and laurylsulfuric acid. Salts with physiologicallyunacceptable acids, e.g. picrates, can be used for the isolation and/orpurification of the compounds of the formula I.

On the other hand, compounds of the formula I can be converted usingbases (e.g. sodium or potassium hydroxide or carbonate) into thecorresponding metal salts, in particular alkali metal salts or alkalineearth metal salts, or into the corresponding ammonium salts.

The compounds of the formula I can contain one or more centers ofasymmetry. In this case, they usually exist in racemic form. Racemateswhich are obtained can be separated into their enantiomers mechanicallyor chemically by methods known per se. Preferably, diastereomers areformed from the racemic mixture by reaction with an optically activeresolving agent.

Of course, it is also possible to obtain optically active compounds ofthe formula I by the methods described above by using startingsubstances which are already optically active.

The present invention furthermore relates to the use of the compounds ofthe formula I and/or their physiologically acceptable salts for theproduction of pharmaceutical preparations, in particular in anon-chemical way. In this connection, they can be brought into asuitable dose form together with at least one solid, liquid and/orsemiliquid excipient or auxiliary and if appropriate in combination withone or more further active compounds.

The invention furthermore relates to pharmaceutical preparationscomprising at least one compound of the formula I and/or one of itsphysiologically acceptable salts.

These preparations can be used as medicaments in human or veterinarymedicine. Suitable excipients are organic or inorganic substances whichare suitable for enteral (e.g. oral) administration or parenteral ortopical application and do not react with the novel compounds, forexample water, vegetable oils, benzyl alcohols, alkylene glycols,polyethylene glycols, glycerol triacetate, gelatine, carbohydrates suchas lactose or starch, magnesium stearate, talc and petroleum jelly.Tablets, pills, coated tablets, capsules, powders, granules, syrups,juices or drops are used for oral administration, suppositories are usedfor rectal administration, solutions, preferably oily or aqueoussolutions, furthermore suspensions, emulsions or implants, are used forparenteral administration and ointments, creams or powders are used fortopical application. The novel compounds can also be lyophilized and thelyophilizates obtained used, for example, for the production ofinjection preparations. The preparations indicated can be sterilizedand/or contain auxiliaries such as lubricants, preservatives,stabilizers and/or wetting agents, emulsifiers, salts for effecting theosmotic pressure, buffer ,substances, colourants, flavorings and/or oneor more further active compounds, e.g. one or more vitamins.

The compounds of the formula I and their physiologically acceptablesalts can be used in the control of illnesses, in particular ofhypertension and cardiac insufficiency.

In this case, the substances according to the invention are generallypreferably administered in doses of between approximately 1 and 500 mg,in particular between 5 and 100 mg per dose unit. The daily dose ispreferably between approximately 0.02 and 10 mg/kg of body weight. Thespecific dose for each patient depends, however, on all sorts offactors, for example on the efficacy of the specific compound employed,on the age, body weight, general state of health, sex, on the diet, onthe time and route of administration, on the excretion rate,pharmaceutical substances combination and severity of the particulardisorder to which the therapy applies. Oral administration is preferred.

Above and below, all temperatures are indicated in °C. In the followingexamples, "customary working up" means: if necessary, water is added, ifnecessary, depending on the constitution of the final product, themixture is adjusted to a pH of between 2 and 10 and extracted with ethylacetate or dichloromethane, the organic phase is separated off, driedover sodium sulfate and evaporated, and the residue is purified bychromatography on silica gel and/or by crystallization. Rf values onsilica gel: eluent: ethyl acetate/methanol 9:1.

Mass spectrometry (MS): EI (electron impact ionization) M⁺

FAB (fast atom bombardment) (M+H)⁺

EXAMPLE 1

3.3 g of caesium carbonate are added to a solution of 1.55 g of2,3-dihydro-4,6-dimethylpyridazin-3-one (prepared according to F. H.McMillan et al., J. Am.Chem. Soc. 78, 407 (1956)) and 4.52 g of2-(1,3-benzodioxol-5-yl)-2-bromo-N-(4-isopropylphenylsulfonyl)acetamidein 100 ml of DMF. The mixture is stirred at room temperature for 2 hoursand worked up in the customary manner and2-(1,3-benzodioxol-5-yl)-2-(2,3-dihydro-4,6-dimethylpyridazin-3-on-2-yl)N-(4-isopropylphenylsulfonyl)acetamideis obtained, m.p. 105°.

Analogously, by reaction of methyl benzo 1,3!dioxol-5-ylbromoacetatewith

6-phenyl-2,3,4,5-tetrahydropyridazin-3-one

6-(4-methoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-one

6-(4-chlorophenyl)-2,3,4,5-tetrahydropyridazin-3-one

6-(4-ethoxycarbonylphenyl)-2,3,4,5-tetrahydropyridazin-3-one

6-methoxycarbonyl-2,3,4,5-tetrahydropyridazine-3-one

6-(2,5-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-one

6-(3,4-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-one

6-(2,4-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-one

6-(thien-2-yl)-2,3,4,5-tetrahydropyridazin-3-one

6-(furan-2-yl)-2,3,4,5-tetrahydropyridazin-3-one

6-phenyl-4-methyl-2,3,4,5-tetrahydropyridazin-3-one

6-(4-methoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-one

6-(4-chlorophenyl)-4-methyl-2,3,4,5,-tetrahydropyridazin-3-one

6-(4-ethoxycarbonylphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-one

6-(2,5-dimethoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-one

6-(3,4-dimethoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-one

6-(thien-2-yl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-one

6-(furan-2-yl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-one

6-methyl-2,3,4,5-tetrahydropyridazin-3-one

4,4,6-trimethyl-2,3,4,5-tetrahydropyridazin-3-one

4,6-dimethyl-2,3,4,5-tetrahydropyridazin-3-one

6-phenyl-2,3-dihydropyridazin-3-one

5-phenyl-6-methyl-2,3-dihydropyridazin-3-one

4-phenyl-6-methyl-2,3-dihydropyridazin-3-one

6-(4-methoxyphenyl)-2,3-dihydropyridazin-3-one

6-(4-chlorophenyl)-2,3-dihydropyridazin-3-one

6-(4-methoxycarbonylphenyl)-2,3-dihydropyridazin-3-one

6-(2,5-dimethoxyphenyl)-2,3-dihydropyridazin-3-one

6-(3,4-dimethoxyphenyl)-2,3-dihydropyridazin-3-one

6-(thien-2-yl)-2,3-dihydropyridazin-3-one

6-(furan-2-yl)-2,3-dihydropyridazin-3-one

6-phenyl-4-methyl-2,3-dihydropyridazin-3-one

6-(4-methoxyphenyl)-4-methyl-2,3-dihydropyridazin-3-one

6-(4-chlorophenyl)-4-methyl-2,3-dihydropyridazin-3-one

6-(4-chlorophenyl)-5-methyl-2,3-dihydropyridazin-3-one

6-(4-ethoxycarbonylphenyl)-4-methyl-2,3-dihydropyridazin-3-one

6-(2,5-dimethoxyphenyl)-4-methyl-2,3-dihydropyridazin-3-one

6-(3,4-dimethoxyphenyl)-4-methyl-2,3-dihydropyridazin-3-one

6-(thien-2-yl)-4-methyl-2,3-dihydropyridazin-3-one

6- (furan-2-yl)-4-methyl-2,3-dihydropyridazin-3-one

6-methyl-2,3-dihydropyridazin-3-one

6-propyl-2,3-dihydropyridazin-3-one

4,6-dimethyl-2,3-dihydropyridazin-3-one

4-propyl-6- methyl-2,3-dihydropyridazin-3-one

4-ethyl-6-methyl-2,3-dihydropyridazin-3-one

4-methyl-6-ethyl-2,3-dihydropyridazin-3-one

4-methyl-6-propyl-2,3-dihydropyridazin-3-one

5,6-dimethyl-2,3-dihydropyridazin-3-one

4,5,6-trimethyl-2,3-dihydropyridazin-3-one

4-methyl-2,3-dihydropyridazin-3-one

5-(4-methoxyphenyl)-2H-3,6-dihydro-1,3,4-thiadiazin-2-one

5-(3,4-dimethoxyphenyl)-6-ethyl-2H-3,6-dihydro-1,3,4-thiadiazin-2-one

6-(4-methanesulfonylphenyl)-2,3,4,5-tetrahydropyridazin-3-one

2,3-dihydropyridazin-3-one

4-(4-methoxybenzyl)-6-methyl-2,3-dihydropyridazin-3-one

6-tert.-butyl-2,3-dihydropyridazin-3-one

6-cyclopropyl-2,3-dihydropyridazin-3-one

the methyl 2-(1,3-benzodioxol-5-yl)-2-(T-yl)acetates below are obtained,

in which T is

6-phenyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-methoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-chlorophenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-ethoxycarbonylphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-methoxycarbonyl-2,3,4,5-tetrahydropyridazine-3-on-2

6-(2,5-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(2,4-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(thien-2-yl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(furan-2-yl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-phenyl-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-methoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-chlorophenyl)-4-methyl-2,3,4,5,-tetrahydropyridazin-3-on-2

6-(4-ethoxycarbonylphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(2,5-dimethoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6- (3,4-dimethoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(thien-2-yl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(furan-2-yl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

4,4,6-trimethyl-2,3,4,5-tetrahydropyridazin-3-on-2

4,6-dimethyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-phenyl-2,3-dihydropyridazin-3-on-2

5-phenyl-6-methyl-2,3-dihydropyridazin-3-one-2

4-phenyl-6-methyl-2,3-dihydropyridazin-3-one-2

6-(4-methoxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(4-chlorophenyl)-2,3-dihydropyridazin-3-on-2

6-(4-methoxycarbonylphenyl)-2,3-dihydropyridazin-3-on-2-6-(2,5-dimethoxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(thien-2-yl)-2,3-dihydropyridazin-3-on-2

6-(furan-2-yl)-2,3-dihydropyridazin-3-on-2

6-phenyl-4-methyl-2,3-dihydropyridazin-3-on-2

6-(4-methoxyphenyl)-4-methyl -2,3-dihydropyridazin-3-on-2

6-(4-chlorophenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(4-chlorophenyl)-5-methyl-2,3-dihydropyridazin-3-on-2

6-(4-ethoxycarbonylphenyl)-4-methyl-2,3-dihydro-pyridazin-3-on-2

6-(2, 5-dimethoxyphenyl) -4-methyl-2,3-dihydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(thien-2-yl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(furan-2-yl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-methyl-2,3-dihydropyridazin-3-on-2

6-propyl-2,3-dihydropyridazin-3-one-2

4,6-dimethyl-2,3-dihydropyridazin-3-on-2, EI 316

4-propyl-6-methyl-2,3-dihydropyridazin-3-on-2

4-ethyl-6-methyl-2,3-dihydropyridazin-3-one-2

4-methyl-6-ethyl-2,3-dihydropyridazin-3-one-2

4-methyl-6-propyl-2,3-dihydropyridazin-3-on-2

5,6-dimethyl-2,3-dihydropyridazin-3-on-2

4,5,6-trimethyl-2,3-dihydropyridazin-3-on-2

4-methyl-2,3-dihydropyridazin-3-on-2

5-(4-methoxyphenyl)-2H-3,6-dihydro-1,3, 4-thiadiazin-2-on-3

5-(3,4-dimethoxyphenyl)-6-ethyl-2H-3, 6-dihydro-1,3,4-thiadiazin-2-on-3

6-(4-methanesulfonylphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

2,3-dihydropyridazin-3-one-2

4-(4-methoxybenzyl)-6-methyl-2,3-dihydropyridazin-3-one-2

6-tert.-butyl-2,3-dihydropyridazin-3-one-2

6-cyclopropyl-2,3-dihydropyridazin-3-one-2.

EXAMPLE 2

A solution of 2.24 g of methyl2-(1,3-benzodioxol-5-yl)-2-(4,6-dimethyl-2,3-dihydropyridazin-3-on-2-yl)-acetatein 20 ml of methanol is treated with 7.08 ml of 1N sodium hydroxidesolution and the mixture is stirred at room temperature for 18 hours. Itis worked up in the customary manner and2-(1,3-benzodioxol-5-yl)-2-(4,6-dimethyl-2,3-dihydropyridazin-3-on-2-yl)aceticacid is obtained, m.p. 165°, EI 302.

Analogously, by hydrolysis of the methyl 2-(1,3-benzodioxol-5-yl)-2-(T-yl)acetates below,

in which T is

6-phenyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-methoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-chlorophenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-ethoxycarbonylphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-methoxycarbonyl-2,3,4,5-tetrahydropyridazine-3-on-2

6-(2,5-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(2,4-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(thien-2-yl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(furan-2-yl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-phenyl-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-methoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-chlorophenyl)-4-methyl-2,3,4,5,-tetrahydropyridazin-3-on-2

6-(4-ethoxycarbonylphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(2,5-dimethoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(thien-2-yl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(furan-2-yl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

4,4,6-trimethyl-2,3,4,5-tetrahydropyridazin-3-on-2

4,6-dimethyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-phenyl-2,3-dihydropyridazin-3-on-2

5-phenyl-6-methyl-2,3-dihydropyridazin-3-one-2

4-phenyl-6-methyl-2,3-dihydropyridazin-3-one-2

6-(4-methoxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(4-chlorophenyl)-2,3-dihydropyridazin-3-on-2

6-(4-methoxycarbonylphenyl)-2,3-dihydropyridazin-3-on-2

6-(2,5-dimethoxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(thien-2-yl)-2,3-dihydropyridazin-3-on-2

6-(furan-2-yl)-2,3-dihydropyridazin-3-on-2

6-phenyl-4-methyl-2,3-dihydropyridazin-3-on-2

6-(4-methoxyphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(4-chlorophenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(4-chlorophenyl)-5-methyl-2,3-dihydropyridazin-3-on-2

6-(4-ethoxycarbonylphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(2,5-dimethoxyphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(thien-2-yl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(furan-2-yl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-methyl-2,3-dihydropyridazin-3-on-2

6-propyl-2,3-dihydropyridazin-3-one-2

4-propyl-6-methyl-2,3-dihydropyridazin-3-on-2

4-ethyl-6-methyl-2,3-dihydropyridazin-3-one-2

4-methyl-6-ethyl-2,3-dihydropyridazin-3-one-2

4-methyl-6-propyl-2,3-dihydropyridazin-3-on-2

5,6-dimethyl-2,3-dihydropyridazin-3-on-2

4,5,6-trimethyl-2,3-dihydropyridazin-3-on-2

4-methyl-2,3-dihydropyridazin-3-on-2

5-(4-methoxyphenyl)-2H-3,6-dihydro-1,3,4-thiadiazin-2-on-3

5-(3,4-dimethoxyphenyl)-6-ethyl-2H-3,6-dihydro-1,3,4-thiadiazin-2-on-3

6-(4-methanesulfonylphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

2,3-dihydropyridazin-3-one-2

4-(4-methoxybenzyl)-6-methyl-2,3-dihydropyridazin-3-one-2

6-tert.-butyl-2,3-dihydropyridazin-3-one-2

6-cyclopropyl-2,3-dihydropyridazin-3-one-2,

the 2-(1,3-benzodioxol-5-yl)-2-(T-yl)acetic acids below are obtained,

in which T is

6-phenyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-methoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2, m.p. 181°

6-(4-chlorophenyl)-2,3,4,5-tetrahydropyridazin-3-on-2, m.p. 168°

6-(4-carboxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2, m.p. 184°

6-carboxy-2,3,4,5-tetrahydropyridazine-3-one, m.p. 178°

6-(2,5-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2, m.p.149.degree.

6-(3,4-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2, m.p.decomposition, FAB 413

6-(2,4-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-one

6-(thien-2-yl)-2,3,4,5-tetrahydropyridazin-3-on-2, m.p. 110°

6-(furan-2-yl)-2,3,4,5-tetrahydropyridazin-3-on-2, FAB 343

6-phenyl-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2, diastereomermixture, FAB 367

6-(4-methoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-chlorophenyl)-4-methyl-2,3,4,5,-tetrahydropyridazin-3-on-2

6-(4-carboxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(2,5-dimethoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(thien-2-yl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(furan-2-yl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

4,4,6-trimethyl-2,3,4,5-tetrahydropyridazin-3-on-2

4,6-dimethyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-phenyl-2,3-dihydropyridazin-3-on-2

5-phenyl-6-methyl-2,3-dihydropyridazin-3-one-2

4-phenyl-6-methyl-2,3-dihydropyridazin-3-one-2

6-(4-methoxyphenyl)-2,3-dihydropyridazin-3-on-2, m.p. 164°

6-(4-chlorophenyl)-2,3-dihydropyridazin-3-on-2

6-(4-carboxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(2,5-dimethoxyphenyl)-2,3-dihydropyridazin-3-on-2

6- (3,4-dimethoxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(thien-2-yl)-2,3-dihydropyridazin-3-on-2

6-(furan-2-yl)-2,3-dihydropyridazin-3-on-2

6-phenyl-4-methyl-2,3-dihydropyridazin-3-on-2, m.p. 125° C.

6-(4-methoxyphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2, FAB 395

6-(4-chlorophenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(4-chlorophenyl)-5-methyl-2,3-dihydropyridazin-3-on-2 m.p. 171°

6-(4-carboxyphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(2,5-dimethoxyphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(thien-2-yl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(furan-2-yl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-methyl-2,3-dihydropyridazin-3-on-2, m.p. 213°

6-propyl-2,3-dihydropyridazin-3-one-2, m.p. 177°

4-propyl-6-methyl-2,3-dihydropyridazin-3-on-2, EI 330

4-ethyl-6-methyl-2,3-dihydropyridazin-3-one-2, m.p. 159°

4-methyl-6-ethyl-2,3-dihydropyridazin-3-one-2, m.p. 106°

4-methyl-6-propyl-2,3-dihydropyridazin-3-on-2, m.p. 225°

5,6-dimethyl-2,3-dihydropyridazin-3-on-2, m.p. 199°

4,5,6-trimethyl-2,3-dihydropyridazin-3-on-2, m.p. 184°

4-methyl-2,3-dihydropyridazin-3-on-2

5-(4-methoxyphenyl)-2H-3,6-dihydro-1,3,4-thiadiazin-2-on-3, m.p.139.degree.

5-(3,4-dimethoxyphenyl)-6-ethyl-2H-3,6-dihydro-1,3, 4-thiadiazin-2-on-3,sodium salt, m.p. 216°

b 6-(4-methanesulfonylphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

2,3-dihydropyridazin-3-one-2, FAB 275

4-(4-methoxybenzyl)-6-methyl-2,3-dihydropyridazin-3-one-2, FAB 409

6-tert.-butyl-2,3-dihydropyridazin-3-one-2, m.p. 179°

6-cyclopropyl-2,3-dihydropyridazin-3-one-2, m.p. 204°.

EXAMPLE 3

A solution of 0.8 g of 2-(1,3-benzodioxol-5-yl)-2-(4,6-dimethyl-2,3-dihydropyridazin-3-on-2-yl)acetic acid and 0.64 g ofcarbonyldiimidazole in 50 ml of THF is heated at 60° for 2 hours. 0.79 gof 4-isopropylbenzenesulfonamide and 0.59 g of 1, 8-diazabicyclo5.4.0!undec-7-ene are then added and the mixture is stirred at thistemperature for a further 1 hour. After customary working up,2-(1,3-benzodioxol-5-yl)-2-(4,6-dimethyl-2,3-dihydropyridazin-3-on-2-yl)N-(4-isopropylphenylsulfonyl)acetamide is obtained, m.p. 105°.

Analogously, by reaction of 4-isopropylbenzenesulfonamide with the2-(1,3-benzodioxol-5-yl)-2-(T-yl)acetic acids below,

in which T is

6-phenyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-methoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-chlorophenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-carboxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-carboxy-2,3,4,5-tetrahydropyridazine-3-on-2

6-(2,5-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(2,4-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-one

6-(thien-2-yl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(furan-2-yl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-phenyl-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-methoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-chlorophenyl)-4-methyl-2,3,4,5,-tetrahydropyridazin-3-on-2

6-(4-carboxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(2,5-dimethoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(thien-2-yl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(furan-2-yl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

4,4,6-trimethyl-2,3,4,5-tetrahydropyridazin-3-on-2

4,6-dimethyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-phenyl-2,3-dihydropyridazin-3-on-2

5-phenyl-6-methyl-2,3-dihydropyridazin-3-one-2

6-(4-methoxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(4-chlorophenyl)-2,3-dihydropyridazin-3-on-2

6-(4-carbonylphenyl)-2,3-dihydropyridazin-3-on-2

6-(2,5-dimethoxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(thien-2-y) -2,3-dihydropyridazin-3-on-2

6-(furan-2-yl)-2,3-dihydropyridazin-3-on-2

6-phenyl-4-methyl-2,3-dihydropyridazin-3-on-2

6-(4-methoxyphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(4-chlorophenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(4-chlorophenyl)-5-methyl-2,3-dihydropyridazin-3-on-2

6-(4-carboxylphenyl)-4-methyl-2,3-dihydropyridazin-3 -on-2

6-(2,5-dimethoxyphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(thien-2-yl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(furan-2-yl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-methyl-2,3-dihydropyridazin-3-on-2

6-propyl-2,3-dihydropyridazin-3-one-2

4-propyl-6-methyl-2,3-dihydropyridazin-3-on-2

4-ethyl-6-methyl-2,3-dihydropyridazin-3-one-2

4-methyl-6-propyl-2,3-dihydropyridazin-3-on-2

5,6-dimethyl-2,3-dihydropyridazin-3-on-2

4,5,6-trimethyl-2,3-dihydropyridazin-3-on-2

4-methyl-2,3-dihydropyridazin-3-on-2

5-(4-methoxyphenyl)-2H-3,6-dihydro-1,3,4-thiadiazin-2-on-3

5-(3,4-dimethoxyphenyl)-6-ethyl-2H-3,6-dihydro-1,3,4-thiadiazin-2-on-3

4,6-dimethyl-2,3-dihydropyridazin-3-one-2

4-(4-methoxybenzyl)-6-methyl-2,3-dihydropyridazin-3-one-2

6-tert.-butyl-2,3-dihydropyridazin-3-one-2

6-cyclopropyl-2,3-dihydropyridazin-3-one-2,

the following2-(1,3-benzodioxol-5-yl)-2-(T-yl)N-(4-isopropylphenylsulfonyl)acetamidesare obtained,

in which T is

6-phenyl-2,3,4,5-tetrahydropyridazin-3-on-2, m.p. 187°

6-(4-methoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2, FAB 564

6-(4-chlorophenyl)-2,3,4,5-tetrahydropyridazin-3-on-2, FAB 568

6-(4-carboxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-carboxy-2,3,4,5-tetrahydropyridazine-3-one

6-(2,5-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2, m.p.187.degree.

6-(3,4-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2, m.p.223.degree.

6-(2,4-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-one, FAB 594

6-(thien-2-yl)-2,3,4,5-tetrahydropyridazin-3-on-2, m.p. 190°

6-(furan-2-yl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-phenyl-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-methoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-chlorophenyl)-4-methyl-2,3,4,5,-tetrahydropyridazin-3-on-2

6-(4-carboxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(2,5-dimethoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(thien-2-yl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(furan-2-yl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-methyl-2,3,4,5-tetrahydropyridazin-3-on-2, FAB 470

4,4,6-trimethyl-2,3,4,5-tetrahydropyridazin-3-on-2

4,6-dimethyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-phenyl-2,3-dihydropyridazin-3-on-2

5-phenyl-6-methyl-2,3-dihydropyridazin-3-one-2

6-(4-methoxyphenyl)-2,3-dihydropyridazin-3-on-2, m.p. 164°

6-(4-chlorophenyl)-2,3-dihydropyridazin-3-on-2

6-(4-carboxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(2,5-dimethoxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(thien-2-yl)-2,3-dihydropyridazin-3-on-2

6-(furan-2-yl)-2,3-dihydropyridazin-3-on-2

6-phenyl-4-methyl-2,3-dihydropyridazin-3-on-2, m.p. 196°

6-(4-methoxyphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2, FAB 579

6-(4-chlorophenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(4-chlorophenyl)-5-methyl-2,3-dihydropyridazin-3-on-2

6-(4-carboxyphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(2,5-dimethoxyphenyl)-4-methyl-2,3-dihydro-pyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(thien-2-yl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(furan-2-yl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-methyl-2,3-dihydropyridazin-3-on-2, m.p.>250°(decomposition)

6-propyl-2,3-dihydropyridazin-3-one-2, FAB 498

4-propyl-6-methyl-2,3-dihydropyridazin-3-on-2

4-ethyl-6-methyl-2,3-dihydropyridazin-3-one-2, m.p. 198°

4-methyl-6-propyl-2,3-dihydropyridazin-3-on-2, m.p. 210°

5,6-dimethyl-2,3-dihydropyridazin-3-on-2, m.p. 194°

4,5,6-trimethyl-2,3-dihydropyridazin-3-on-2

4-methyl-2,3-dihydropyridazin-3-on-2

5-(4-methoxyphenyl)-2H-3,6-dihydro-1,3,4-thiadiazin-2-on-3

5-(3,4-dimethoxyphenyl)-6-ethyl-2H-3,6-dihydro-1,3,4-thiadiazin-2-on-3

4,6-dimethyl-2,3-dihydropyridazin-3-one-2, FAB 484; potassium salt FAB522

4-(4-methoxybenzyl)-6-methyl-2,3-dihydropyridazin-3-one-2, FAB 590

6-tert.-butyl-2,3-dihydropyridazin-3-one-2, FAB 511

6-cyclopropyl-2,3-dihydropyridazin-3-one-2, FAB 496.

Analogously, by reaction of 4-tert-butylbenzenesulfonamide with the2-(1,3-benzodioxol-5-yl)-2-(T-yl)-acetic acids below,

in which T is

6-phenyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-methoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-chlorophenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-carboxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-carboxy-2,3,4,5-tetrahydropyridazine-3-on-2

6-(2,5-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(2,4-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-one

6-(thien-2-yl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-phenyl-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-methoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-chlorophenyl)-4-methyl-2,3,4,5,-tetrahydropyridazin-3-on-2

6-(4-carboxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(2,5-dimethoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(thien-2-yl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

4,4,6-trimethyl-2,3,4,5-tetrahydropyridazin-3-on-2

4,6-dimethyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-phenyl-2,3-dihydropyridazin-3-on-2

6-(4-methoxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(4-chlorophenyl)-2,3-dihydropyridazin-3-on-2

6-(4-carboxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(2,5-dimethoxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(thien-2-yl)-2,3-dihydropyridazin-3-on-2

6-phenyl-4-methyl-2,3-dihydropyridazin-3-on-2

6-(4-methoxyphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(4-chlorophenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(4-chlorophenyl)-5-methyl-2,3-dihydropyridazin-3-on-2

6-(4-carboxyphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(2,5-dimethoxyphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(thien-2-yl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-methyl-2,3-dihydropyridazin-3-on-2

4,6-dimethyl-2,3-dihydropyridazin-3-on-2

4-propyl-6-methyl-2,3-dihydropyridazin-3-on-2

4-methyl-6-propyl-2,3-dihydropyridazin-3-on-2

5,6-dimethyl-2,3-dihydropyridazin-3-on-2

4,5,6-trimethyl-2,3-dihydropyridazin-3-on-2

4-methyl- 2,3-dihydropyridazin-3-on-2

5-(4-methoxyphenyl)-2H-3,6-dihydro-1,3,4-thiadiazin-2-on-3

5-(3,4-dimethoxyphenyl)-6-ethyl-2H-3, 6-dihydro-1,3,4-thiadiazin-2-on-3,

the following2-(1,3-benzodioxol-5-yl)-2-(T-yl)N-(4-tert-butylsulfonyl)acetamides areobtained,

in which T is

6-phenyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-methoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2, m.p. 213°

6-(4-chlorophenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-carboxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-carboxy-2,3,4,5-tetrahydropyridazine-3-on-2

6-(2,5-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(2,4-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-one

6-(thien-2-yl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-phenyl-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-methoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-chlorophenyl)-4-methyl-2,3,4,5,-tetrahydropyridazin-3-on-2

6-(4-carboxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(2,5-dimethoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(thien-2-yl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

4,4,6-trimethyl-2,3,4,5-tetrahydropyridazin-3-on-2

4,6-dimethyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-phenyl-2,3-dihydropyridazin-3-on-2

6-(4-methoxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(4-chlorophenyl)-2,3-dihydropyridazin-3-on-2

6-(4-carboxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(2,5-dimethoxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(thien-2-yl)-2,3-dihydropyridazin-3-on-2

6-phenyl-4-methyl-2,3-dihydropyridazin-3-on-2

6-(4-methoxyphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(4-chlorophenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(4-chlorophenyl )-5-methyl-2,3-dihydropyridazin-3-on-2

6-(4-carboxyphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(2,5-dimethoxyphenyl) -4-methyl-2,3-dihydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(thien-2-yl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-methyl-2,3-dihydropyridazin-3-on-2, FAB 484

4,6-dimethyl-2,3-dihydropyridazin-3-on-2, FAB 498

4-propyl-6-methyl-2,3-dihydropyridazin-3-on-2

4-methyl-6-propyl-2,3-dihydropyridazin-3-on-2

5,6-dimethyl-2,3-dihydropyridazin-3-on-2

4,5,6-trimethyl-2,3-dihydropyridazin-3-on-2

4-methyl-2,3-dihydropyridazin-3-on-2

5-(4-methoxyphenyl)-2H-3,6-dihydro-1,3,4-thiadiazin-2-on-3

5-(3,4-dimethoxyphenyl)-6-ethyl-2H-3,6-dihydro-1,3,4-thiadiazin-2-on-3.

Analogously, by reaction of 4-methoxybenzenesulfonamide with the2-(1,3-benzodioxol-5-yl)-2-(T-yl)acetic acids below,

in which T is

6-phenyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-methoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-chlorophenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-carboxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-carboxy-2,3,4,5-tetrahydropyridazine-3-one

6-(2,5-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(2,4-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-one

6-(thien-2-yl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-phenyl-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-methoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-chlorophenyl)-4-methyl-2,3,4,5,-tetrahydropyridazin-3-on-2

6-(4-carboxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(2,5-dimethoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(thien-2-yl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

4,4,6-trimethyl-2,3,4,5-tetrahydropyridazin-3-on-2

4,6-dimethyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-phenyl-2,3-dihydropyridazin-3-on-2

6-(4-methoxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(4-chlorophenyl)-2,3-dihydropyridazin-3-on-2

6-(4-carboxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(2,5-dimethoxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(thien-2-yl)-2,3-dihydropyridazin-3-on-2

6-phenyl-4-methyl-2,3-dihydropyridazin-3-on-2

6-(4-methoxyphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(4-chlorophenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(4-chlorophenyl)-5-methyl-2,3-dihydropyridazin-3-on-2

6-(4-carboxyphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(2,5-dimethoxyphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(thien-2-yl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-methyl-2,3-dihydropyridazin-3-on-2

4,6-dimethyl-2,3-dihydropyridazin-3-on-2

4-propyl-6-methyl-2,3-dihydropyridazin-3-on-2

4-methyl-6-propyl-2,3-dihydropyridazin-3-on-2

5,6-dimethyl-2,3-dihydropyridazin-3-on-2

4,5,6-trimethyl-2,3-dihydropyridazin-3-on-2

4-methyl-2,3-dihydropyridazin-3-on-2

5-(4-methoxyphenyl)-2H-3,6-dihydro-1,3,4-thiadiazin-2-on-3

5-(3,4-dimethoxyphenyl)-6-ethyl-2H-3,6-dihydro-1,3,4-thiadiazin-2-on-3,

the following2-(1,3-benzodioxol-5-yl)-2-(T-yl)N-(4-methoxyphenylsulfonyl)acetamidesare obtained,

in which T is

6-phenyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-methoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-chlorophenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-carboxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-carboxy-2,3,4,5-tetrahydropyridazine-3-one

6-(2,5-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-(2,4-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-one

6-(thien-2-yl)-2,3,4,5-tetrahydropyridazin-3-on-2

6-phenyl-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-methoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(4-chlorophenyl)-4-methyl-2,3,4,5,-tetrahydropyridazin-3-on-2

6-(4-carboxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(2,5-dimethoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-(thien-2-yl)-4-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-methyl-2,3,4,5-tetrahydropyridazin-3-on-2

4,4,6-trimethyl-2,3,4,5-tetrahydropyridazin-3-on-2

4,6-dimethyl-2,3,4,5-tetrahydropyridazin-3-on-2

6-phenyl-2,3-dihydropyridazin-3-on-2

6-(4-methoxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(4-chlorophenyl)-2,3-dihydropyridazin-3-on-2

6-(4-carboxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(2,5-dimethoxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-2,3-dihydropyridazin-3-on-2

6-(thien-2-yl)-2,3-dihydropyridazin-3-on-2

6-phenyl-4-methyl-2,3-dihydropyridazin-3-on-2

6-(4-methoxyphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(4-chlorophenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(4-chlorophenyl)-5-methyl-2,3-dihydropyridazin-3-one

6-(4-carboxyphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(2,5-dimethoxyphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(3,4-dimethoxyphenyl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-(thien-2-yl)-4-methyl-2,3-dihydropyridazin-3-on-2

6-methyl-2,3-dihydropyridazin-3-on-2, FAB 458

4,6-dimethyl-2,3-dihydropyridazin-3-on-2, EI 471

4-propyl-6-methyl-2,3-dihydropyridazin-3-on-2

4-methyl-6-propyl-2,3-dihydropyridazin-3-on-2

5,6-dimethyl-2,3-dihydropyridazin-3-on-2

4,5,6-trimethyl-2,3-dihydropyridazin-3-on-2

4-methyl-2,3-dihydropyridazin-3-on-2

5-(4-methoxyphenyl)-2H-3,6-dihydro-1,3, 4-thiadiazin-2-on-3

5-(3,4-dimethoxyphenyl)-6-ethyl-2H-3,6-dihydro-1,3,4-thiadiazin-2-on-3.

EXAMPLE 4

Analogously to Example 1, by reaction of 4,6-dimethyl-2,3-dihydropyridazin-3-one with the following methylM-bromoacetates,

in which M is

phenyl

1,4-benzodioxan-5-yl

1,3-benzodioxol-4-yl

2-methoxyphenyl

3-methoxyphenyl

4-methoxyphenyl

2-methoxycarbonylphenyl

3-methoxycarbonylphenyl

4-methoxycarbonylphenyl

2,3-dimethoxyphenyl

2,4-dimethoxyphenyl

2,5-dimethoxyphenyl

3,4-dimethoxyphenyl

3,5-dimethoxyphenyl

4-cyanophenyl

2,1,3-benzothiadiazol-5-yl

2,1,3-benzooxadiazol-5-yl

5-dimethylaminonaphthyl

2- difluoromethoxy phenyl

3-difluoromethoxyphenyl

4-difluoromethoxyphenyl

4-methyl-2,1,3-benzothiadiazol-5-yl

4-trifluoromethyl-2,1,3-benzothiadiazol-5-yl

7-bromo-2,1,3-benzothiadiazol-5-yl

4-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl

4-chloro-2,1,3-benzooxadiazol-5-yl

6-nitro-2,1,3-benzooxadiazol-5-yl

4-bromo-6-tert-butyl-2,1,3-benzooxadiazol-5-yl

4-cyano-2,1,3-benzooxadiazol-5-yl

2,1,3-benzothiadiazol-4- yl

2-methoxycarbonylmethoxy-4-methoxyphenyl

the following methyl 2-(M)-2- (4,6-dimethyl-2,3-dihydropyridazin-3-on-2-yl) acetates are obtained,

in which M is

phenyl

1,4-benzodioxan-5-yl

1,3-benzodioxol-4-yl

2-methoxyphenyl

3-methoxyphenyl

4-methoxyphenyl

2-methoxycarbonylphenyl

3-methoxycarbonylphenyl

4-methoxycarbonylphenyl

2,3-dimethoxyphenyl

2,4-dimethoxyphenyl

2,5-dimethoxyphenyl

3,4-dimethoxyphenyl

3,5-dimethoxyphenyl

4-cyanophenyl

2,1,3-benzothiadiazol-5-yl

2,1,3-benzooxadiazol-5-yl

5-dimethylaminonaphthyl

2-difluoromethoxyphenyl

3-difluoromethoxyphenyl

4-difluoromethoxyphenyl

4-methyl-2,1,3-benzothiadiazol-5-yl

4-trifluoromethyl-2,1,3-benzothiadiazol-5-yl

7-bromo-2,1,3-benzothiadiazol-5-yl

4-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl

4-chloro-2,1,3-benzooxadiazol-5-yl

6-nitro-2,1,3-benzooxadiazol-5-yl

4-bromo-6-tert-butyl-2,1,3-benzooxadiazol-5-yl

4-cyano-2,1,3-benzooxadiazol-5-yl

2,1,3-benzothiadiazol-4-yl

2-methoxycarbonylmethoxy-4-methoxyphenyl.

Analogously, by reaction of6-(4-methoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-one with the followingmethyl M-bromoacetates,

in which M is

phenyl

1,4-benzodioxan-5-yl

1,3-benzodioxol-4-yl

2-methoxyphenyl

3-methoxyphenyl

4-methoxyphenyl

2-methoxycarbonylphenyl

3-methoxycarbonylphenyl

4-methoxycarbonylphenyl

2,3-dimethoxyphenyl

2,4-dimethoxyphenyl

2,5-dimethoxyphenyl

3,4-dimethoxyphenyl

3,5-dimethoxyphenyl

4-cyanophenyl

2,1,3-benzothiadiazol-5-yl

2,1,3-benzooxadiazol-5-yl

5-dimethylaminonaphthyl

2-difluoromethoxyphenyl

3-difluoromethoxyphenyl

4-difluoromethoxyphenyl

4-methyl-2,1,3-benzothiadiazol-5-yl

4-trifluoromethyl-2,1,3-benzothiadiazol-5-yl

7-bromo-2,1,3-benzothiadiazol-5-yl

4-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl

4-chloro-2,1,3-benzooxadiazol-5-yl

6-nitro-2,1,3-benzooxadiazol-5-yl

4-bromo-6-tert-butyl-2,1,3-benzooxadiazol-5-yl

4-cyano-2,1,3-benzooxadiazol-5-yl

2,1,3-benzothiadiazol-4-yl

2-methoxycarbonylmethoxy-4-methoxyphenyl,

the following methyl 2-(M)-2-(6-(4-methoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2-yl)acetates are obtained,

in which M is

phenyl

1,4-benzodioxan-5-yl

1,3-benzodioxol-4-yl

2-methoxyphenyl

3-methoxyphenyl

4-methoxyphenyl

2-methoxycarbonylphenyl

3-methoxycarbonylphenyl

4-methoxycarbonylphenyl

2,3-dimethoxyphenyl

2,4-dimethoxyphenyl

2,5-dimethoxyphenyl

3,4-dimethoxyphenyl

3,5-dimethoxyphenyl

4-cyanophenyl

2,1,3-benzothiadiazol-5-yl

2,1,3-benzooxadiazol-5-yl

5-dimethylaminonaphthyl

2-difluoromethoxyphenyl

3-difluoromethoxyphenyl

4-difluoromethoxyphenyl

4-methyl-2,1,3-benzothiadiazol-5-yl

4-trifluoromethyl-2,1,3-benzothiadiazol-5-yl

7-bromo-2,1,3-benzothiadiazol-5-yl

4-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl

4-chloro-2,1,3-benzooxadiazol-5-yl

6-nitro-2,1,3-benzooxadiazol-5-yl

4-bromo-6-tert-butyl-2,1,3-benzooxadiazol-5-yl

4-cyano-2,1,3-benzooxadiazol-5-yl

2,1,3-benzothiadiazol-4-yl

2-methoxycarbonylmethoxy-4-methoxyphenyl.

Analogously, by reaction of6-(4-chlorophenyl)-2,3,4,5-tetrahydropyridazin-3-one with the followingmethyl M-bromoacetates,

in which M is

phenyl

1,4-benzodioxan-5-yl

1,3-benzodioxol-4-yl

2-methoxyphenyl

3-methoxyphenyl

4-methoxyphenyl

2-methoxycarbonylphenyl

3-methoxycarbonylphenyl

4-methoxycarbonylphenyl

2,3-dimethoxyphenyl

2,4-dimethoxyphenyl

2,5-dimethoxyphenyl

3,4-dimethoxyphenyl

3,5-dimethoxyphenyl

4-cyanophenyl

2,1,3-benzothiadiazol-5-yl

2,1,3-benzooxadiazol-5-yl

5-dimethylaminonaphthyl

2-difluoromethoxyphenyl

3-difluoromethoxyphenyl

4-difluoromethoxyphenyl

4-methyl-2,1,3-benzothiadiazol-5-yl

4-trifluoromethyl-2,1,3-benzothiadiazol-5-yl

7-bromo-2,1,3-benzothiadiazol-5-yl

4-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl

4-chloro-2,1,3-benzooxadiazol-5-yl

6-nitro-2,1,3-benzooxadiazol-5-yl

4-bromo-6-tert-butyl-2,1,3-benzooxadiazol-5-yl

4-cyano-2,1,3-benzooxadiazol-5-yl

2,1,3-benzothiadiazol-4-yl

2-methoxycarbonylmethoxy-4-methoxyphenyl,

the following methyl-2-(M)-2-(6-(4-chlorophenyl)-2,3,4,5-tetrahydropyridazin-3-on-2-yl)acetates are obtained

in which M is

phenyl

1,4-benzodioxan-5-yl

1,3-benzodioxol-4-yl

2-methoxyphenyl

3-methoxyphenyl

4-methoxyphenyl

2-methoxycarbonylphenyl

3-methoxycarbonylphenyl

4-methoxycarbonylphenyl

2,3-dimethoxyphenyl

2,4-dimethoxyphenyl

2,5-dimethoxyphenyl

3,4-dimethoxyphenyl

3,5-dimethoxyphenyl

4-cyanophenyl

2,1,3-benzothiadiazol-5-yl

2,1,3-benzooxadiazol-5-yl

5-dimethylaminonaphthyl

2-difluoromethoxyphenyl

3-difluoromethoxyphenyl

4-difluoromethoxyphenyl

4-methyl-2,1,3-benzothiadiazol-5-yl

4-trifluoromethyl-2,1,3-benzothiadiazol-5-yl

7-bromo-2,1,3-benzothiadiazol-5-yl

4-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl

4-chloro-2,1,3-benzooxadiazol-5-yl

6-nitro-2,1,3-benzooxadiazol-5-yl

4-bromo-6-tert-butyl-2,1,3-benzooxadiazol-5-yl

4-cyano-2,1,3-benzooxadiazol-5-yl

2,1,3-benzothiadiazol-4-yl

2-methoxycarbonylmethoxy-4-methoxyphenyl.

Analogously, by reaction of 6- (3,4-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-one with the following methylM-bromoacetates,

in which M is

phenyl

1,4-benzodioxan-5-yl

1,3-benzodioxol-4-yl

2-methoxyphenyl

3-methoxyphenyl

4-methoxyphenyl

2-methoxycarbonylphenyl

3-methoxycarbonylphenyl

4-methoxycarbonylphenyl

2,3-dimethoxyphenyl

2,4-dimethoxyphenyl

2,5-dimethoxyphenyl

3,4-dimethoxyphenyl

3,5-dimethoxyphenyl

4-cyanophenyl

2,1,3-benzothiadiazol-5-yl

2,1,3-benzooxadiazol-5-yl

5-dimethylaminonaphthyl

2-difluoromethoxyphenyl

3-difluoromethoxyphenyl

4-difluoromethoxyphenyl

4-methyl-2,1,3-benzothiadiazol-5-yl

4-trifluoromethyl-2,1,3-benzothiadiazol-5-yl

7-bromo-2,1,3-benzothiadiazol-5-yl

4-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl

4-chloro-2,1,3-benzooxadiazol-5-yl

6-nitro-2,1,3-benzooxadiazol-5-yl

4-bromo-6-tert-butyl-2,1,3-benzooxadiazol-5-yl

4-cyano-2,1,3-benzooxadiazol-5-yl

2,1,3-benzothiadiazol-4-yl

2-methoxycarbonylmethoxy-4-methoxyphenyl,

the following methyl2-(M)-2-(6-(3,4-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2-yl)acetatesare obtained,

in which M is

phenyl

1,4-benzodioxan-5-yl

1,3-benzodioxol-4-yl

2-methoxyphenyl

3-methoxyphenyl

4-methoxyphenyl

2-methoxycarbonylphenyl

3-methoxycarbonylphenyl

4-methoxycarbonylphenyl

2,3-dimethoxyphenyl

2,4-dimethoxyphenyl

2,5-dimethoxyphenyl

3,4-dimethoxyphenyl

3,5-dimethoxyphenyl

4-cyanophenyl

2,1,3-benzothiadiazol-5-yl

2,1,3-benzooxadiazol-5-yl

5-dimethylaminonaphthyl

2-difluoromethoxyphenyl

3-difluoromethoxyphenyl

4-difluoromethoxyphenyl

4-methyl-2,1,3-benzothiadiazol-5-yl

4-trifluoromethyl-2,1,3-benzothiadiazol-5-yl

7-bromo-2,1,3-benzothiadiazol-5-yl

4-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl

4-chloro-2,1,3-benzooxadiazol-5-yl

6-nitro-2,1,3-benzooxadiazol-5-yl

4-bromo-6-tert-butyl-2,1,3-benzooxadiazol-5-yl

4-cyano-2,1,3-benzooxadiazol-5-yl

2,1,3-benzothiadiazol-4-yl

2-methoxycarbonylmethoxy-4-methoxyphenyl.

EXAMPLE 5

Analogously to Example 2, by hydrolysis of the following

methyl 2-(M)-2-(4,6-dimethyl-2,3-dihydropyridazin-3-on-2-yl)acetates,

methyl2-(M)-2-(6-(4-methoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2-yl)acetates

methyl2-(M)-2-(6-(4-chlorophenyl)-2,3,4,5-tetrahydropyridazin-3-on-2-yl)acetatesand

methyl2-(M)-2-(6-(3,4-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2-yl)acetates,

in which M is

phenyl

1,4-benzodioxan-5-yl

1,3-benzodioxol-4-yl

2-methoxyphenyl

3-methoxyphenyl

4-methoxyphenyl

2-methoxycarbonylphenyl

3-methoxycarbonylphenyl

4-methoxycarbonylphenyl

2,3-dimethoxyphenyl

2,4-dimethoxyphenyl

2,5-dimethoxyphenyl

3,4-dimethoxyphenyl

3,5-dimethoxyphenyl

4-cyanophenyl

2,1,3-benzothiadiazol-5-yl

2,1,3-benzooxadiazol-5-yl

5-dimethylaminonaphthyl

2-difluoromethoxyphenyl

3-difluoromethoxyphenyl

4-difluoromethoxyphenyl

4-methyl-2,1,3-benzothiadiazol-5-yl

4-trifluoromethyl-2,1,3-benzothiadiazol -5-yl

7-bromo-2,1,3-benzothiadiazol-5-yl

4-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl

4-chloro-2,1,3-benzooxadiazol-5-yl

6-nitro-2,1,3-benzooxadiazol-5-yl

4-bromo-6-tert-butyl-2,1,3-benzooxadiazol-5-yl

4-cyano-2,1,3-benzooxadiazol-5-yl

2,1,3-benzothiadiazol-4-yl

2-methoxycarbonylmethoxy-4-methoxyphenyl,

the following

2-(M)-2-(4,6-dimethyl-2,3-dihydropyridazin-3-on-2-yl)-acetic acids,

in which M is

phenyl

1,4-benzodioxan-5-yl

1,3-benzodioxol-4-yl

2-methoxyphenyl

3-methoxyphenyl

4-methoxyphenyl, m.p. 204°

2- methoxycarbonylphenyl

3-methoxycarbonylphenyl

4-methoxycarbonylphenyl

2,3-dimethoxyphenyl

2,4-dimethoxyphenyl

2,3-dimethoxyphenyl

3,4-dimethoxyphenyl

3,5-dimethoxyphenyl

4- cyanophenyl

2,1,3-benzothiadiazol-5-yl

2,1,3-benzooxadiazol-5-yl

5-dimethylaminonaphthyl

2- difluoromethoxyphenyl

3-difluoromethoxyphenyl

4-difluoromethoxyphenyl

4-methyl-2,1,3-benzothiadiazol-5-yl

4-trifluoromethyl-2,1,3-benzothiadiazol-5-yl

7-bromo-2,1,3-benzothiadiazol-5-yl

4-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl

4-chloro-2,1,3-benzooxadiazol-5-yl

6-nitro-2,1,3-benzooxadiazol-5-yl

4-bromo-6-tert-butyl-2,1,3-benzooxadiazol-5-yl

4-cyano-2,1,3-benzooxadiazol-5-yl

2,1,3-benzothiadiazol-4-yl

2-carboxymethoxy-4-methoxyphenyl,

2-(M)-2-(-(4-methoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2-yl)acetic acids,

in which M is

phenyl

1 4-benzodioxan-5-yl

1,3-benzodioxol-4-yl

2-methoxyphenyl

3-methoxyphenyl

4-methoxyphenyl

2-methoxycarbonylphenyl

3-methoxycarbonylphenyl

4-methoxycarbonylphenyl

2,3-dimethoxyphenyl

2,4-dimethoxyphenyl

2,5-dimethoxyphenyl

3,4-dimethoxyphenyl

3,5-dimethoxyphenyl

4-cyanophenyl

2,1,3-benzothiadiazol-5-yl

2,1,3-benzooxadiazol-5-yl

5-dimethylaminonaphthyl

2-difluoromethoxyphenyl

3-difluoromethoxyphenyl

4-difluoromethoxyphenyl

4-methyl-2,1,3-benzothiadiazol-5-yl

4-trifluoromethyl-2,1,3-benzothiadiazol-5-yl

7-bromo-2,1,3-benzothiadiazol-5-yl

4-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl

4-chloro-2,1,3-benzooxadiazol-5-yl

6-nitro-2,1,3-benzooxadiazol-5-yl

4-bromo-6-tert-butyl-2,1,3-benzooxadiazol-5-yl

4-cyano-2,1,3-benzooxadiazol-5-yl

2,1,3-benzothiadiazol-4-yl

2-methoxycarbonylmethoxy-4-methoxyphenyl,

2-(M)-2-(6-(4-chlorophenyl)-2,3,4,5-tetrahydropyridazin-3-on-2-yl)aceticacids,

in which M is

phenyl

1,4-benzodioxan-5-yl

1,3-benzodioxol-4-yl

2-methoxyphenyl

3-methoxyphenyl

4-methoxyphenyl

2-methoxycarbonylphenyl

3-methoxycarbonylphenyl

4-methoxycarbonylphenyl

2,3 -dimethoxyphenyl

2,4-dimethoxyphenyl

2,5-dimethoxyphenyl

3,4-dimethoxyphenyl

3,5-dimethoxyphenyl

4-cyanophenyl

2,1,3-benzothiadiazol-5-yl

2,1,3-benzooxadiazol-5-yl

5-dimethylaminonaphthyl

2-difluoromethoxyphenyl

3-difluoromethoxyphenyl

4-difluoromethoxyphenyl

4-methyl-2,1,3-benzothiadiazol-5-yl

4-trifluoromethyl-2,1,3-benzothiadiazol-5-yl

7-bromo-2,1,3-benzothiadiazol-5-yl

4-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl

4-chloro-2,1,3-benzooxadiazol-5-yl

6-nitro-2,1,3-benzooxadiazol-5-yl

4-bromo-6-tert-butyl-2,1,3-benzooxadiazol-5-yl

4-cyano-2,1,3-benzooxadiazol-5-yl

2,1,3-benzothiadiazol-4-yl

2-carboxymethoxy-4-methoxyphenyl,

and

2-(M)-2- (6-(3,4-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2-yl) acetic acids,

in which M is

phenyl

1,4-benzodioxan- 5-yl

1,3-benzodioxol-4-yl

2-methoxyphenyl

3-methoxyphenyl

4-methoxyphenyl

2-methoxycarbonylphenyl

3-methoxycarbonylphenyl

4-methoxycarbonylphenyl

2,3-dimethoxyphenyl

2,4-dimethoxyphenyl

2,5-dimethoxyphenyl

3,4-dimethoxyphenyl

3,5-dimethoxyphenyl

4-cyanophenyl

2,1,3-benzothiadiazol-5-yl

2,1,3-benzooxadiazol-5-yl

5-dimethylaminonaphthyl

2-difluoromethoxyphenyl

3-difluoromethoxyphenyl

4-difluoromethoxyphenyl

4-methyl-2,1,3-benzothiadiazol-5-yl

4-trifluoromethyl-2,1,3-benzothiadiazol-5-yl

7-bromo-2,1,3-benzothiadiazol-5-yl

4-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl

4-chloro-2,1,3-benzooxadiazol-5-yl

6-nitro-2,1,3-benzooxadiazol-5-yl

4-bromo-6-tert-butyl-2,1,3-benzooxadiazol-5-yl

4-cyano-2,1,3-benzooxadiazol-5-yl

2,1,3-benzothiadiazol-4-yl

2-carboxymethoxy-4-methoxyphenyl, are obtained.

EXAMPLE 6

Analogously to Example 3, by reaction of 4-isopropylbenzenesulfonamidewith the

2-(M)-2-(4,6-dimethyl-2,3-dihydropyridazin-3-on-2-yl)-acetic acids,

2-(M)-2-(6-(4-methoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2-yl)aceticacids,

2-(M)-2-(6-(4-chlorophenyl)-2,3,4,5-tetrahydropyridazin-3-on-2-yl)aceticacids, and

2-(M)-2-(6-(3,4-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2-yl)aceticacids below,

in which M is

phenyl

1,4-benzodioxan-5-yl

1,3-benzodioxol-4-yl

2-methoxyphenyl

3-methoxyphenyl

4-methoxyphenyl

2-methoxycarbonylphenyl

3-methoxycarbonylphenyl

4-methoxycarbonylphenyl

2,3-dimethoxy phenyl

2,4-dimethoxyphenyl

2,5-dimethoxyphenyl

3,4-dimethoxyphenyl

3,5-dimethoxyphenyl

4-cyanophenyl

2,1,3-benzothiadiazol-5-yl

2,1,3-benzooxadiazol-5-yl

5-dimethylaminonaphthyl

2-difluoromethoxyphenyl

3-difluoromethoxyphenyl

4-difluoromethoxyphenyl

4-methyl-2,1,3-benzothiadiazol -5-yl

4-trifluoromethyl-2,1,3-benzothiadiazol -5-yl

7-bromo-2,1,3-benzothiadiazol-5-yl

4-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl

4-chloro-2,1,3-benzooxadiazol-5-yl

6nitro-2,1,3-benzooxadiazol-5-yl

4-bromo-6-tert-butyl-2,1,3-benzooxadiazol-5-yl

4-cyano-2,1,3-benzooxadiazol-5-yl

2,1,3- benzothiadiazol-4-yl

2-carboxymethoxy-4-methoxyphenyl,

the following

2-(M)-2-(4,6-dimethyl-2,3-dihydropyridazin-3-on-2-yl)-N-(4-isopropylphenylsulfonyl)acetamides,

in which M is

phenyl

1,4-benzodioxan-5-yl

1,3-benzodioxol-4-yl

2-methoxyphenyl

3-methoxyphenyl

4-methoxyphenyl, m.p. 275° (decomposition)

2-methoxycarbonylphenyl

3-methoxycarbonylphenyl

4-methoxycarbonylphenyl

2,3-dimethoxyphenyl

2,4-dimethoxyphenyl

2,5-dimethoxyphenyl

3,4-dimethoxyphenyl

3,5-dimethoxyphenyl

4-cyanophenyl

2,1,3-benzothiadiazol-5-yl

2,1,3-benzooxadiazol-5-yl

5-dimethylaminonaphthyl

2-difluoromethoxyphenyl

3-difluoromethoxyphenyl

4-difluoromethoxyphenyl

4-methyl-2,1,3-benzothiadiazol-5-yl

4-trifluoromethyl-2,1,3-benzothiadiazol-5-yl

7-bromo-2,1,3-benzothiadiazol-5-yl

4-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl

4-chloro-2,1,3-benzooxadiazol-5-yl

6-nitro-2,1,3-benzooxadiazol-5-yl

4-bromo-6-tert-butyl-2,1,3-benzooxadiazol-5-yl

4-cyano-2,1,3-benzooxadiazol-5-yl

2,1,3-benzothiadiazol-4-yl

2-carboxymethoxy-4-methoxyphenyl,

2-(M)-2-(6-(4-methoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2-yl)N-(4-isopropylphenylsulfonyl)-acetamides,

in which M is

phenyl

1,4-benzodioxan-5-yl

1,3-benzodioxol-4-yl

2-methoxyphenyl

3-methoxyphenyl

4-methoxyphenyl

2-methoxycarbonylphenyl

3-methoxycarbonylphenyl

4-methoxycarbonylphenyl

2,3-dimethoxyphenyl

2,4-dimethoxyphenyl

2,5-dimethoxyphenyl

3,4-dimethoxyphenyl

3,5-dimethoxyphenyl

4-cyanophenyl

2,1,3-benzothiadiazol-5-yl

2,1,3-benzooxadiazol-5-yl

5-dimethylaminonaphthyl

2-difluoromethoxyphenyl

3-difluoromethoxyphenyl

4-difluoromethoxyphenyl

4-methyl-2,1,3-benzothiadiazol-5-yl

4-trifluoromethyl-2,1,3-benzothiadiazol-5-yl

7-bromo-2,1,3-benzothiadiazol-5-yl

4-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl

4-chloro-2,1,3-benzooxadiazol-5-yl

6-nitro-2,1,3-benzooxadiazol-5-yl

4-bromo-6-tert-butyl-2,1,3-benzooxadiazol-5-yl

4-cyano-2,1,3-benzooxadiazol-5-yl

2,1,3-benzothiadiazol-4-yl

2-carboxymethoxy-4-methoxyphenyl,

2-(M)-2-(6-(4-chlorophenyl)-2,3,4,5-tetrahydropyridazin-3-on-2-yl)N-(4-isopropylphenylsulfonyl)-acetamides,

in which M is

phenyl

1,4-benzodioxan-5-yl

1,3-benzodioxol-4-yl

2-methoxyphenyl

3-methoxyphenyl

4-methoxyphenyl

2-methoxycarbonylphenyl

3-methoxycarbonylphenyl

4-methoxycarbonylphenyl

2,3-dimethoxyphenyl

2,4-dimethoxyphenyl

2,5-dimethoxyphenyl

3,4-dimethoxyphenyl

3,5-dimethoxyphenyl

4-cyanophenyl

2,1,3-benzothiadiazol-5-yl

2,1,3-benzooxadiazol-5-yl

5-dimethylaminonaphthyl

2-difluoromethoxyphenyl

3-difluoromethoxyphenyl

4-difluoromethoxyphenyl

4-methyl-2,1,3-benzothiadiazol-5-yl

4-trifluoromethyl-2,1,3-benzothiadiazol-5-yl

7-bromo-2,1,3-benzothiadiazol-5-yl

4-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl

4-chloro-2,1,3-benzooxadiazol-5-yl

6-nitro-2,1,3-benzooxadiazol-5-yl

4-bromo-6-tert-butyl-2,1,3-benzooxadiazol-5-yl

4-cyano-2,1,3-benzooxadiazol-5-yl

2,1,3-benzothiadiazol-4-yl

2-carboxymethoxy-4-methoxyphenyl,

and

2-(M)-2-(6-(3,4-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2-yl)N-(4-isopropylphenylsulfonyl)-acetamides,

in which M is

phenyl

1,4-benzodioxan-5-yl

1,3-benzodioxol-4-yl

2-methoxyphenyl

3-methoxyphenyl

4-methoxyphenyl

2-methoxycarbonylphenyl

3-methoxycarbonylphenyl

4-methoxycarbonylphenyl

2,3-dimethoxyphenyl

2,4-dimethoxyphenyl

2,5-dimethoxyphenyl

3,4-dimethoxyphenyl

3,5-dimethoxyphenyl

4-cyanophenyl

2,1,3-benzothiadiazol-5-yl

2,1,3-benzooxadiazol-5-yl

5-dimethylaminonaphthyl

2-difluoromethoxyphenyl

3-difluoromethoxyphenyl

4-difluoromethoxyphenyl

4-methyl-2,1,3-benzothiadiazol-5-yl

4-trifluoromethyl-2,1,3-benzothiadiazol-5-yl

7-bromo-2,1,3-benzothiadiazol-5-yl

4-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl

4-chloro-2,1,3-benzooxadiazol-5-yl

6-nitro-2,1,3-benzooxadiazol-5-yl

4-bromo-6-tert-butyl-2,1,3-benzooxadiazol-5-yl

4-cyano-2,1,3-benzooxadiazol-5-yl

2,1,3-benzothiadiazol-4-yl

2-carboxymethoxy-4-methoxyphenyl,

are obtained.

Analogously, by reaction of 4-tert-butylbenzenesulfonamide with theabovementioned acetic acid derivatives the

2-(M)-2-(4,6-dimethyl-2,3-dihydropyridazin-3-on-2-yl)-N-(4-tert-butylphenylsulfonyl)acetamidesbelow,

in which M is

phenyl

1,4-benzodioxan-5-yl

1,3-benzodioxol-4-yl

2-methoxyphenyl

3-methoxyphenyl

4-methoxyphenyl

2-methoxycarbonylphenyl

3-methoxycarbonylphenyl

4-methoxycarbonylphenyl

2,3-dimethoxyphenyl

2,4-dimethoxyphenyl

2,5-dimethoxyphenyl

3,4-dimethoxyphenyl

3,5-dimethoxyphenyl

4-cyanophenyl

2,1,3-benzothiadiazol-5-yl

2,1,3-benzooxadiazol-5-yl

5-dimethylaminonaphthyl

2-difluoromethoxyphenyl

3-difluoromethoxyphenyl

4-difluoromethoxyphenyl

4-methyl-2,1,3-benzothiadiazol-5-yl

4-trifluoromethyl-2,1,3-benzothiadiazol-5-yl

7-bromo-2,1,3-benzothiadiazol-5-yl

4-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl

4-chloro-2,1,3-benzooxadiazol-5-yl

6-nitro-2,1,3-benzooxadiazol-5-yl

4-bromo-6-tert-butyl-2,1,3-benzooxadiazol-5-yl

4-cyano-2,1,3-benzooxadiazol-5-yl

2,1,3-benzothiadiazol-4-yl

2-carboxymethoxy-4-methoxyphenyl

2-(M)-2-(6-(4-methoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2-yl)N-(4-tert-butylphenylsulfonyl)-acetamides,

in which M is

phenyl

1,4-benzodioxan-5-yl

1,3-benzodioxol-4-yl

2-methoxyphenyl

3-methoxyphenyl

4-methoxyphenyl

2-methoxycarbonylphenyl

3-methoxycarbonylphenyl

4-methoxycarbonylphenyl

2,3-dimethoxyphenyl

2,4-dimethoxyphenyl

2,5-dimethoxyphenyl

3,4-dimethoxyphenyl

3,5-dimethoxyphenyl

4-cyanophenyl

2,1,3-benzothiadiazol-5-yl

2,1,3-benzooxadiazol-5-yl

5-dimethylaminonaphthyl

2-difluoromethoxyphenyl

3-difluoromethoxyphenyl

4-difluoromethoxyphenyl

4-methyl-2,1,3-benzothiadiazol-5-yl

4-trifluoromethyl-2,1,3-benzothiadiazol-5-yl

7-bromo-2,1,3-benzothiadiazol-5-yl

4-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl

4-chloro-2,1,3-benzooxadiazol-5-yl

6-nitro-2,1,3-benzooxadiazol-5-yl

4-bromo-6-tert-butyl-2,1,3-benzooxadiazol-5-yl

4-cyano-2,1,3-benzooxadiazol-5-yl

2,1,3-benzothiadiazol-4-yl

2-carboxymethoxy-4-methoxyphenyl

2-(M)-2-(6-(4-chlorophenyl)-2,3,4,5-tetrahydropyridazin-3-on-2-yl)N-(4-tert-butylphenylsulfonyl)-acetamides,

in which M is

phenyl

1,4-benzodioxan-5-yl

1,3-benzodioxol-4-yl

2-methoxyphenyl

3-methoxyphenyl

4-methoxyphenyl

2-methoxycarbonylphenyl

3-methoxycarbonylphenyl

4-methoxycarbonylphenyl

2,3-dimethoxyphenyl

2,4-dimethoxyphenyl

2,5-dimethoxyphenyl

3,4-dimethoxyphenyl

3,5-dimethoxyphenyl

4-cyanophenyl

2,1,3-benzothiadiazol-5-yl

2,1,3-benzooxadiazol-5-yl

5-dimethylaminonaphthyl

2-difluoromethoxyphenyl

3-difluoromethoxyphenyl

4-difluoromethoxyphenyl

4-methyl-2,1,3-benzothiadiazol-5-yl

4-trifluoromethyl-2,1,3-benzothiadiazol-5-yl

7-bromo-2,1,3-benzothiadiazol-5-yl

4-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl

4-chloro-2,1,3-benzooxadiazol-5-yl

6-nitro-2,1,3-benzooxadiazol-5-yl

4-bromo-6-tert-butyl-2,1,3-benzooxadiazol-5-yl

4-cyano-2,1,3-benzooxadiazol-5-yl

2,1,3-benzothiadiazol-4-yl

2-carboxymethoxy-4-methoxyphenyl

and

2-(M)-2-(6-(3,4-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2-yl)N-(4-tert-butylphenylsulfonyl)-acetamides,

in which M is

phenyl

1,4-benzodioxan-5-yl

1,3-benzodioxol-4-yl

2-methoxyphenyl

3-methoxyphenyl

4-methoxyphenyl

2-methoxycarbonylphenyl

3-methoxycarbonyphenyl

4-methoxycarbonylphenyl

2,3-dimethoxyphenyl

2,4-dimethoxyphenyl

2,5-dimethoxyphenyl

3,4-dimethoxyphenyl

3,5-dimethoxyphenyl

4-cyanophenyl

2,1,3-benzothiadiazol-5-yl

2,1,3-benzooxadiazol-5-yl

5-dimethylaminonaphthyl

2-difluoromethoxyphenyl

3-difluoromethoxyphenyl

4-difluoromethoxyphenyl

4-methyl-2,1,3-benzothiadiazol-5-yl

4-trifluoromethyl-2,1,3-benzothiadiazol-5-yl

7-bromo-2,1,3-benzothiadiazol-5-yl

4-ethoxycarbonyl-2,1,3-benzothiadiazol-5-yl

4-chloro-2,1,3-benzooxadiazol-5-yl

6-nitro-2,1,3-benzooxadiazol-5-yl

4-bromo-6-tert-butyl-2,1,3-benzooxadiazol-5-yl

4-cyano-2,1,3-benzooxadiazol-5-yl

2,1,3-benzothiadiazol-4-yl

2-carboxymethoxy-4-methoxyphenyl,

are obtained.

EXAMPLE 7

Analogously to Example 3, by reaction of(5-dimethylaminonaphthyl)-sulfonamide with2-(1,3-benzodioxol-5-yl)-2-(6-methyl-2,3-dihydropyridazin-3-on-2-yl)aceticacid ("A") the compound 2-(1,3-benzodioxol-5-yl)-2-(6-methyl-2,3-dihydropyridazin-3-on-2-yl)-N-(5-dimethylaminonaphthyl-sulfonyl)acetamideis obtained, FAB 521.

Analogously, by reaction of "A"

with benzenesulfonamide

2-(1,3-benzodioxol-5-yl)-2-(6-methyl-2,3-dihydropyridazin-3-on-2-yl)-N-(phenylsulfonyl)acetamide, EI 427, isobtained, and

with 4-bromo-benzenesulfonamide

2-(1,3-benzodioxol-5-yl)-2-(6-methyl-2,3-dihydropyridazin-3-on-2-yl)-N-(4-bromophenylsulfonyl)-acetamide,FAB 506, is obtained,

and with biphenylsulfonamide

2-(1,3-benzodioxol-5-yl)-2-(6-methyl-2,3-dihydropyridazin-3-on-2-yl)-N-(biphenylsulfonyl)acetamide,FAB 504, is obtained.

EXAMPLE 8

Analogously to Example 1 and 2, by reaction of methyl benzo1,3!dioxol-5-ylbromoacetate ("B") with6-(pyridine-2-yl)-2,3-dihydropyridazin-3-one and subsequent hydrolysisthe compound

2-(1,3-benzodioxol-5-yl)-2-(6-(pyridine-2-yl)-2,3-dihydropyridazin-3-on-2-yl)aceticacid, m.p. 115°, is obtained,

and by reaction of methyl(4-methoxyphenyl)-bromoacetate with4-(4-methoxybenzyl)-6-methyl-2,3-dihydropyridazin-3-one and subsequenthydrolysis the compound

2-(4-methoxyphenyl)-2-(4-(4-methoxybenzyl)-6-methyl-2,3-dihydro-pyridazin-3-on-2-yl)aceticacid, EI 408, is obtained,

and by reaction of "B" with4-(4-methoxybenzyl)-6-(4-methoxyphenyl)-2,3-dihydropyridazin-3-one andsubsequent hydrolysis the compound

2-(1,3-benzodioxol-5-yl)-2-(4-(4-methoxybenzyl)-6-(4-methoxyphenyl)-2,3-dihydropyridazin-3-on-2-yl)aceticacid is obtained.

Analogously,2-(1,3-benzodioxol-5-yl)-2-(4-(2-methoxybenzyl)-6-(4-methoxyphenyl)-2,3-dihydropyridazin-3-on-2-yl)aceticacid, FAB 501, is obtained,

and by reaction of "B" with 6-trifluoromethyl-2,3-dihydropyridazin-3-oneand subsequent hydrolysis the compound

2-(1,3-benzodioxol-5-yl)-2-(6-trifluoromethyl-2,3-dihydropyridazin-3-on-2-yl)aceticacid, FAB 343, is obtained.

Analogously, by reaction of "B" with4-phenyl-6-cyclopropyl-2,3-dihydro-pyridazin-3-on and subsequenthydrolysis the compound

2-(1,3-benzodioxol-5-yl)-2-(4-phenyl-6-cyclopropyl-2,3-dihydropyridazin-3-on-2-yl)aceticacid, m.p. 176°, is obtained.

The following examples relate to pharmaceutical preparations:

Example A: Injection vials

A solution of 100 g of an active compound of the formula I and 5 g ofdisodium hydrogen phosphate are adjusted to pH 6.5 in 3 l ofdouble-distilled water using 2N hydrochloric acid, sterile-filtered,filled into injection vials, lyophilized under sterile conditions andasceptically sealed. Each injection vial contains 5 mg of activecompound.

Example B: Suppositories

A mixture of 20 g of an active compound of the formula I is fused with100 g of soya lecithin and 1400 g of cocoa butter, poured into molds andallowed to cool. Each suppository contains 20 mg of active compound.

Example C: Solution

A solution of 1 g of an active compound of the formula I, 9.38 g of NaH₂PO₄.2H₂ O, 28.48 g of Na₂ HPO₄.12H₂ O and 0.1 g of benzalkonium chloridein 940 ml of double-distilled water is prepared. The mixture is adjustedto pH 6.8, made up to 1 l and sterilized by irradiation. This solutioncan be used in the form of eye drops.

Example D: Ointment

500 mg of an active compound of the formula I is mixed with 99.5 g ofpetroleum jelly under aseptic conditions.

Example E: Tablets

A mixture of 1 kg of active compound of the formula I, 4 kg of lactose,1.2 kg of potato starch, 0.2 kg of talc and 0.1 kg of magnesium stearateis compressed to give tablets in the customary manner such that eachtablet contains 10 mg of active compound.

Example F: Coated tablets

Analogously to Example E, tablets are pressed which are then coated in acustomary manner with a coating of sucrose, potato starch, talc,tragacanth and colorants.

Example G: Capsules

2 kg of active compound of the formula I are formed into hard gelatinecapsules in a customary manner such that each capsule contains 20 mg ofthe active compound.

Example H: Ampoules

A solution of 1 kg of active compound of the formula I in 60 l ofdouble-distilled water is sterile-filtered, filled into ampoules,lyophilized under sterile conditions and aseptically sealed. Eachampoule contains 10 mg of active compound.

We claim:
 1. A compound of formula I ##STR10## wherein Y is --C(R⁴R^(4'))C(R⁴ R^(4')), --CR⁴ ═CR^(4') - or C(R⁴ R⁴)S--,R¹ is Het, Ar, R³or R⁴, R² is Ar or a ##STR11## which is unsubstituted or mono- ordisubstituted in the phenyl moiety by A, R³, OR⁴, NH₂, NHA, NA₂, NO₂,CN, Hal, NHCOR⁴, NHSO₂ R⁴, COOR⁴, COR⁴, CONHSO₂ R⁶, O(CH₂)_(n) R³, OPh,O(CH₂)_(n) OR⁴ or S(O)_(m) R⁴ ora ##STR12## which is unsubstituted ormono- or disubstituted in the cyclohexyldienyl moiety by A, R³, OR⁴,NH₂, NHA, NA₂, NO₂, CN, Hal, NHCOR⁴, NHSO₂ R⁴, COOR⁴, COR⁴, CONHSO₂ R⁶,O(CH₂)_(n) R³, OPh, O(CH₂)_(n) OR⁴ or S(O)_(m) R⁴, R³ is CN, COOH, COOA,CONHSO₂ R⁵ or 1H-tetrazol-5-yl R⁴,R^(4') in each case independently ofone another are H, A or phenyl or benzyl which is unsubstituted ormonosubstituted by alkoxy, R⁵ is A or Ar, R⁶ is phenyl or naphthyl whichis unsubstituted or mono-, di- or trisubstituted by A, OR⁵, NH₂, NHA,NA₂, NO₂ CN or Hal, A is alkyl having 1-6 C atoms, in which one or twoCH₂ groups can be replaced by O or S atoms or by --CR⁴ ═CR⁴ ' groups andalso 1-7 H atoms can be replaced by F or is benzyl, Ar is phenyl ornaphthyl, which is unsubstituted or mono-, di- or trisubstituted by A,OR⁴, NH₂, NHA, NA₂, NO₂, CN, Hal, NHCOR⁴, NHSO₂ R⁴, COOR⁴, COR⁴, CONHSO₂R⁶, O(CH₂)_(n) R³, OPh, O(CH₂)_(n) OR⁴ or S(O)_(m) R⁴, Het is a mono- orbicyclic saturated, unsaturated or aromatic heterocycle having 1 to 4 N,O and/or S atoms, bonded via N or C, which can be unsubstituted ormono-, di- or trisubstituted by Hal, A, R³, NH₂, NHA, NA₂, CN, NO₂and/or carbonyl oxygen, D is carbonyl or _(n), E is CH₂, S or O, Hal isF, Cl, Br or I, X is 0 or S, m is 0, 1 or 2, n is 1 or 2,or a saltthereof, with the proviso that R² is not unsubstituted phenyl.
 2. a)2-(1,3-Benzodioxol-5-yl)-2-(2,3-dihydro-4,6-dimethylpyridazin-3-on-2-yl)N-(4-isopropylphenylsulfonyl)acetamide;b)2-(1,3-benzodioxol-5-yl)-2-(6-(4-methoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2-yl)N-(4-isopropylphenylsulfonyl)-acetamide;c)2-(1,3-benzodioxol-5-yl)-2-(6-(4-chlorophenyl)-2,3,4,5-tetrahydropyridazin-3-on-2-yl)N-(4-isopropylphenylsulfonyl)acetamide;d)2-(1,3-benzodioxol-5-yl)-2-(6-(3,4-dimethoxyphenyl)-2,3,4,5-tetrahydropyridazin-3-on-2-yl)N-(4-isopropylphenylsulfonyl)-acetamide;e)2-(1,3-benzodioxol-5-yl)-2-(4-methyl-6-phenyl-2,3-dihydropyridazin-3-on-2-yl)N-(4-isopropylphenylsulfonyl)acetamide; or f)2-(1,3-benzodioxol-5-yl)-2-(5-(3,4-dimethoxyphenyl)-6-ethyl-2H-3,6-dihydro-1,3,4-thiadiazin-2-on-3-yl)N-(4-isopropylphenylsulfonyl)acetamide, each a compound of claim
 1. 3. A process for preparing acompound of formula I according to claim 1 and a salt thereof,comprisingreacting a compound of formula II ##STR13## wherein R¹ and Yhave the meanings indicated in claim 1, with a compound of formula III##STR14## wherein Q is Cl, Br, I or a free or reactive functionallymodified OH group andR² and R³ have the meanings indicated in claim 1,and/or converting one or more radicals R¹, R² and/or R³ in a compound offormula I into one or more radicals R¹, R² and/or R³ by,i) hydrolysingan ester group to a carboxyl group, ii) converting a carboxyl group intoa sulfonamidocarbonyl group and/or converting a base or acid of acompound of formula I into one of its salts.
 4. A pharmaceuticalpreparation, comprising an effective amount of at least one compound offormula I of claim 1 and/or one of its physiologically acceptable salts,and a pharmaceutically acceptable excipient.
 5. A method of treatinghypertension, cardiac insufficiency, renal insufficiency, cerebralinfarct, coronary heart disease, renal, cerebral and myocardialischaemia, subarachnoid haemorrhage, inflammations, asthma, endotoxicshock in a patient in need of such treatment, comprising administeringan effective amount of a compound of claim 1 or a physiologicallyacceptable salt thereof.